The ROPES research activities were organised into seven work packages (WPs). Three of these were dedicated to scientific discovery (WPs 1–3), while the others focused on training (WP4), dissemination and communication (WP5), coordination (WP6) and ethics management (WP7).
WP1 developed advanced epitranscriptomic methodologies, bioinformatics tools and databases. Significant outcomes included expanding MODOMICS, a major RNA modification database, and creating NACDDB, a unique nucleic acid circular dichroism database. ROPES researchers also developed innovative site-directed RNA editing techniques that can precisely alter gene expression to study disease mechanisms. Notably, they demonstrated the impact of editing Filamin genes on tumour angiogenesis.
WP2 explored the roles of epitranscriptomics in disease onset and progression. They discovered that changes in m6A RNA methylation significantly influence tumour growth and invasiveness in neuroblastoma, breast cancer, and pancreatic adenocarcinoma. In Drosophila models, m5C methylation enzymes were found to be linked to fertility and neurological phenotypes, and RNA editing mechanisms were identified as being crucial in the regulation of innate immune responses.
The aim of WP3 was to translate epitranscriptomic knowledge into therapeutic concepts. This was successfully achieved by identifying promising small molecules that target m6A reader proteins (YTHDF), RNA editing enzymes (ADAR) and poorly studied RNA modifications, such as N1-methylguanine (m1G). Proof-of-concept studies have demonstrated that modifying RNA interactions can reduce tumour aggressiveness and alter disease-relevant pathways, thus confirming the therapeutic potential of RNA modifications.
WPs 4–7 efficiently delivered training, communication, dissemination, project management and ethical oversight, ensuring that ESRs obtained comprehensive skills in scientific and transferable domains. This led to the awarding of PhDs and future employment in high-profile scientific positions.
